Companion Animals as Sentinels
for Predicting Environmental
Exposure Effects on Aging and
Cancer Susceptibility in Humans

__________

Ruth Cooper, Carol Berkower, and
Sharyl Nass, Rapporteurs

National Cancer Policy Forum

Forum on Aging, Disability, and Independence

Board on Health Care Services

Health and Medicine Division

Standing Committee on the Use of
Emerging Science for
Environmental Health Decisions

Division on Earth and Life Studies

Proceedings of a Workshop

THE NATIONAL ACADEMIES PRESS 500 Fifth Street, NW Washington, DC 20001

This activity was supported by the American Kennel Club Canine Health Foundation; Animal Cancer Foundation; College of Veterinary Medicine & Biomedical Science at Texas A&M University; Environmental Protection Agency, Contract No. 68HERC19D0011 (Task Order No. 68HERC22F0077); Flint Animal Cancer Center, Colorado State University; Morris Animal Foundation; National Cancer Institute, Contract No. HHSN263201800029I (Task Order No. HHSN26300008); National Institute of Environmental Health Sciences, Contract No. HHSN263201800029I (Task Order No. 75N98020F0018); National Institute on Aging/National Institutes of Health, Contract No. HHSN2632018000029I (Task Order 75N98019F00848); Nicholas School of the Environment; North Carolina State University College of Veterinary Medicine; and University of Colorado Cancer Center.

International Standard Book Number-13: 978-0-309-68794-2
International Standard Book Number-10: 0-309-68794-2
Digital Object Identifier: https://doi.org/10.17226/26547

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Suggested citation: National Academies of Sciences, Engineering, and Medicine. 2022. Companion animals as sentinels for predicting environmental exposure effects on aging and cancer susceptibility in humans: Proceedings of a workshop. Washington, DC: The National Academies Press. https://doi.org/10.17226/26547.

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PLANNING COMMITTEE ON THE ROLE OF COMPANION ANIMALS AS SENTINELS FOR PREDICTING ENVIRONMENTAL EXPOSURE EFFECTS ON AGING AND CANCER SUSCEPTIBILITY IN HUMANS¹

LINDA S. BIRNBAUM (Chair), Scientist Emeritus, National Institute of Environmental Health Sciences/National Toxicology Program; Scholar in Residence, Nicholas School of the Environment, Duke University

MATTHEW BREEN, Professor of Genomics, Oscar J. Fletcher Distinguished Professor of Comparative Oncology Genetics, Department of Molecular Biomedical Sciences, College of Veterinary Medicine, North Carolina State University

MYRTLE DAVIS, Executive Director, Discovery Toxicology, Bristol Myers Squibb

NICOLE DEZIEL, Associate Professor, Yale School of Public Health, Yale Center for Perinatal, Pediatric, and Environmental Epidemiology

WILLIAM FARLAND, Professor Emeritus, Environmental and Radiological Health Sciences, College of Veterinary Medicine and Biomedical Sciences, Colorado State University

ROY JENSEN, Director, The University of Kansas Cancer Center, Kansas Masonic Cancer Research Institute; William R. Jewell, MD Distinguished Masonic Professor, The University of Kansas Cancer Center, The University of Kansas Medical Center

DANIEL PROMISLOW, Principal Investigator and Co-Director, Dog Aging Project; Professor, Department of Lab Medicine & Pathology and Department of Biology, University of Washington School of Medicine

WENDY SHELTON, Principal, Virtual Beast Consulting; Consultant, Colorado State University

CHERYL LYN WALKER, Alkek Presidential Chair in Environmental Health; Director, Center for Precision Environmental Health; Professor, Departments of Molecular & Cell Biology and Medicine, Baylor College of Medicine

Project Staff

RUTH COOPER, Associate Program Officer

TOCHI OGBU-MBADIUGHA, Senior Program Assistant

___________________

¹ The National Academies of Sciences, Engineering, and Medicine’s planning committees are solely responsible for organizing the workshop, identifying topics, and choosing speakers. The responsibility for the published Proceedings of a Workshop rests with the workshop rapporteurs and the institution.

MARILEE SHELTON DAVENPORT, Senior Program Officer, Standing Committee on the Use of Emerging Science for Environmental Health Decisions (until March 2022)

TRACY A. LUSTIG, Senior Program Officer; Director, Forum on Aging, Disability, and Independence

SHARYL NASS, Senior Director, Board on Health Care Services; Co-Director, National Cancer Policy Forum

Reviewers

This Proceedings of a Workshop was reviewed in draft form by individuals chosen for their diverse perspectives and technical expertise. The purpose of this independent review is to provide candid and critical comments that will assist the National Academies of Sciences, Engineering, and Medicine in making each published proceedings as sound as possible and to ensure that it meets the institutional standards for quality, objectivity, evidence, and responsiveness to the charge. The review comments and draft manuscript remain confidential to protect the integrity of the process.

We thank the following individuals for their review of this proceedings:

Although the reviewers listed above provided many constructive comments and suggestions, they were not asked to endorse the content of the proceedings nor did they see the final draft before its release. The review of this proceedings was overseen by ELI Y. ADASHI, Brown University. He was responsible for making certain that an independent examination of this proceedings was carried out in accordance with standards of the National Academies and that all review comments were carefully considered. Responsibility for the final content rests entirely with the rapporteurs and the National Academies.

We also thank staff member Alexandra Beatty for reading and providing helpful comments on this manuscript.

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Acknowledgments

The National Academies of Sciences, Engineering, and Medicine’s Board on Health Care Services wishes to express its sincere gratitude to the planning committee chair, Linda S. Birnbaum, for her valuable contributions to the development and orchestration of this workshop. The board also wishes to thank all the members of the planning committee, who collaborated to ensure a workshop replete with informative presentations and moderated rich discussions. We are also grateful for the support of our workshop sponsors, without which we could not have undertaken this project, particularly Danielle Carlin, National Institute of Environmental Health Sciences, and Rodney Page, Flint Animal Cancer Center, Colorado State University. Finally, the board wants to thank the speakers, who generously shared their expertise and their time with workshop participants. Research assistance was provided by Christopher Lao-Scott, National Academies.

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Contents

ACRONYMS AND ABBREVIATIONS

PROCEEDINGS OF A WORKSHOP

INTRODUCTION

BACKGROUND ON CANCER, AGING, AND ENVIRONMENTAL EXPOSURE RESEARCH

HISTORY AND CURRENT STATE OF THE SCIENCE OF ENVIRONMENTAL EXPOSURE EFFECTS ON AGING AND CANCER SUSCEPTIBILITY

Environmental Exposure and Cancer

Environmental Exposure, Cancer, and Aging in Companion Animals: The Companion Dog Model

Why Pet Dogs with Spontaneous Tumors are Good Models for Human Disease

How Diet Modulates the Tumor Microenvironment (TME)

Epigenetic Aging as a Target and Biomarker for Environmental Exposures

Domestic Dogs as a System for Understanding Aging and Life Span

Aging, Somatic Evolution, and Cancer—The Inexorable Link

Discussion: Animal Size, Reproductive Status, and Cancer

METHODS AND CURRENT STUDIES

The Exposome and Health

Biomonitoring of Chemical Exposure in Companion Animals and Humans

Ongoing Canine Population Studies

Discussion: Advancing Use of Companion Dogs as Sentinels

RELEVANCE OF COMPANION ANIMAL EXPOSURES TO HUMAN CANCER AND AGING

Exposures to Air Pollution, Smoking, and Lead

Using Silicone Samplers to Assess Air Pollution in People and Pets

Cats as Sentinels for Persistent Organic Pollutants Indoors

Radon Exposures and Cancer in Pets

Heavy Metal Exposures in the Dogs of Chernobyl

Exposures through Food

Chemical Mixtures, Cancer, and Diet—The Example of Pesticides

Discussion: Relevance of Companion Animal Exposures to Humans

ACCELERATING CROSS-SPECIES COMPARISONS: OPPORTUNITIES AND CHALLENGES IN DATA SOURCES, COLLECTION, STORAGE, MODELING, AND SHARING

Human Exposure Assessment

Comparative Oncology: How Dogs are Helping Researchers Understand and Treat Cancer

Biobanks for Companion Animal Sentinel Studies

Using Ontologies to Unify Genomics and Phenomics across Species

Data, Samples, and Modeling

Discussion: Accelerating Cross-Species Comparisons

EQUITY, ETHICS, AND POLICY

Ethical Considerations of Using Companion Animals as Sentinels: Research Subject Protections, Citizen Science Issues, and Shared Health

One Health Approaches in Arctic Indigenous Communities

Aligning Health Care for a Bonded Family Society

Discussion: Equity, Ethics, and Policy

IDENTIFYING RESEARCH GAPS AND SETTING A RESEARCH AGENDA: EXPLORING NEXT STEPS FOR THE PATH FORWARD

Obtaining Data on Pets and Exposures

Interdisciplinary Training of Researchers, Physicians, and Veterinarians for One Health

Translating the Science between Pets and People

Data Integration

Data Collection: Long-Term Investment

Data Collection: Tapping into Existing Cohorts (Short Term)

Continuing and Expanding the Conversation

Community Research—Engagement and Equity

CONCLUDING REMARKS AND POTENTIAL NEXT STEPS

References

APPENDIXES

A STATEMENT OF TASK

B WORKSHOP AGENDA

C BIOGRAPHICAL SKETCHES OF PLANNING COMMITTEE MEMBERS AND WORKSHOP SPEAKERS

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Boxes, Figures, and Table

BOXES

1 Suggestions from Individual Workshop Participants to Advance the Use of Companion Animals as Sentinels for Predicting Environmental Exposure Effects on Aging and Cancer Susceptibility in Humans

2 Examples of NIEHS-Sponsored Sensor Research

3 The Golden Retriever Lifetime Study

4 The Dog Aging Project

5 Studies of Dogs as Sentinels for Testicular Dysgenesis Syndrome

FIGURES

1 Increasing incidence of common cancers and specifically colorectal cancers (CRC): Environmental etiology?

2 The complexities of documenting exposures

3 Dogs can serve as a useful model in comparative oncology

4 The remarkable similarity in cancers that develop in humans and dogs

5 The nonlinear relationship between dog age and human age

6 Cancers requiring different numbers of driver mutations and originating from stem cell pools that are organized in vastly different ways demonstrate very similar age-dependent incidence

7 The exposome: Implications for examining environmental health disparities

8 The exposome concept

9 Approaches to exposure science at the NIEHS

10 Contingency Test for Trend based on (A) associations of body weight and (B) body condition scores with quartile rankings based on serum total PFAS concentrations

11 The Hallmark Framework of cancer progression

12 Comparative molecular features of canine and human osteosarcomas

13 Development of species-agnostic ontologies to classify phenotypes across species

14 Integration of exposure event modeling with the Monarch Knowledge Graph

TABLE

1 A Selection of Canine Cancer Sentinel Studies Showing Positive Association or No Association with Environmental Exposure

Acronyms and Abbreviations